DESCRIPTION (provided by principal investigator): The identification of risk or protective factors associated with cognitive decline, especially ones that may lead to prevention strategy, is critically important. Selenium is a trace element that is considered a defensive agent against free radicals through the maintenance of better enzyme activity. The proposed application is the continuation of a collaborative longitudinal study of rural elderly Chinese age 65 or older aimed at confirming or refuting the hypothesis that long-term low selenium exposure is associated with greater cognitive decline. Since the start of the original project in April 2003, we have enrolled 2000 individuals age 65 and older from four rural Chinese counties and collected data on selenium exposure, cognitive function and other information. Our baseline results showed that low selenium levels were associated with lower cognitive function. We also reported that higher plasma calcium level was associated with higher cognitive scores. Higher plasma cadmium and copper levels, on the other hand, were associated with lower cognitive scores. In addition, there is an intrigue finding that apolipoprotein E (APOE) 54 allele carriers had significantly lower selenium levels measured in nail samples even though the two genotype groups did not differ on dietary intake of selenium. Data from this cohort also reveals that there is a high proportion of undetected hypertension and higher blood pressure measures were associated with greater cognitive decline. We propose to conduct two more evaluations of cognitive function and to collect blood samples from all study participants in order to obtain biomarker measures including lipids, homocysteine, insulin, glucose, interleukin-6 levels as well as other trace element levels including calcium, cadmium and copper. These biomarker measures will allow better characterization of chronic medical conditions and ascertainment of important cardiovascular risk factors in this cohort, thus enabling us to examine whether selenium's association with cognitive decline is independent or interactive with other potential risk factors for cognitive decline and dementia. We will also examine the potential interaction between selenium and apolipoprotein E (APOE) 54 allele on cognitive decline and dementia and determine the association between other trace element levels measured in blood samples and cognitive decline. PUBLIC HEALTH RELEVANCE: The proposed application is the continuation of a longitudinal epidemiologic study aimed at confirming or refuting the hypothesis that long-term low selenium exposure is associated with greater cognitive decline and greater risk for dementia. Selenium exposure is a factor that is easily modifiable by changing dietary habits or through supplements. Our hypotheses, if confirmed, can provide the first evidence supporting long-term selenium as a protective agent against cognitive decline. A preventive measure on cognitive decline, even moderate, can have a significant impact on public health by reducing prevalent cases of cognitive impairment, thus reducing the cost of treating and caring for the impaired. Most importantly, preventive measures for cognitive decline can prolong the state of healthy aging and maintain the quality of life for many elderly individuals in the U.S. and around the world.